Process for producing inorganic porous material in a capillary

ABSTRACT

Inorganic porous materials contained in a confined space with at least one dimension of less than 1 mm, which are in liquid tight contact with the walls of said confined space. Preferred as the confined space are capillaries. Articles contained such materials and methods for making them in the confined space are described.

FIELD OF THE INVENTION

The present invention is related to a process for producing inorganicporous materials in a capillary (or more generally in a confined spaceas defined below) and materials prepared by such process. Thesematerials are favorably applied to producing capillary columns forelectrochromatography, porous catalysts, or enzyme supports. Suchinorganic porous columns can be favorably applied to liquid,gel-permeation and gas chromatography. These columns can be usedunmodified or modified e.g. by covering their surface with moleculeslike hydrophobic hydrocarbon ligands (e.g. octadecyl ligands) or likehydrophilic ligands like 2,3-dihydroxypropyl derivatives. The ligands ofsuch modified columns can be further modified using known procedures.Porous catalysts or enzyme supports can be prepared by adding enzymes,e.g. glucose isomerase, or catalytic metal elements, e.g. platinum andpalladium.

BACKGROUND OF THE INVENTION

The sol-gel method is one of liquid phase reaction paths to produceinorganic porous materials, especially silica gels. The sol-gel methoddenotes widespread processes in which polymerizable low molecular weightspecies are first generated, and through polymerization reactions,aggregated or polymerized materials are finally obtained. For example,the sol-gel method can be applied by hydrolyzing metal alkoxides, metalchlorides, metal salts or coordinated compounds which typically containcarboxyl or beta-diketone ligands. A process of this kind is disclosedin EP 0 363 697. In this process an organic polymer is used, which iscompatible with the solution of the metal alkoxide or its polymer, andwhich undergoes phase separation during the hydrolysis-polymerizationstep. The materials produced by this process display connected openpores with a narrow range of the pore size distribution. Improvements tothe process as disclosed in EP 0 363 697 are subject matter of WO 95/03256 and WO 98/29 350. WO 95/03 256 disclose the use of special poreforming agents, whereas WO 98/29 350 disclose the use of precursors ofsuch pore forming agents. All three documents disclose procedures usefulto produce monolithic porous bodies. Common to the procedures disclosedin these three documents is that the porous formed body produced istaken out of the cast used for forming it. Such a procedure is notamenable if the porous formed body has a small dimension in at least onedirection, because such thin structures would easily be teared or break.On the other hand the procedures disclosed in these three documents donot yield porous bodies which are fit liquid tight to their cast,because the inorganic material shrinks considerably during processing.

The existing capillary columns for electrochromatography is produced bypacking inorganic materials such as silica gel beads into a capillary byphysical means. It is necessary for the column packing materials used inthe electrochromatography to carry electrostatic charge on theirsurfaces. Accordingly, inorganic porous materials which retain stablenegative charges in a neutral pH condition, especially silica gels, arewidely used.

Particle-packed capillary columns for electrochromatography have beenprepared by physically packing inorganic particulate materials into acapillary. In order to avoid the change in the packing state of theparticles due to their motion in the capillary, the both ends of acapillary are fitted with the parts called “frit” with relatively lowporosity.

Particle-packed capillary columns are disadvantageous in the pointsthat: (a) the packing procedure is complicated and time-consuming. (b)the reproducibility of the packing state, and correspondingly that of anexcellent analytical performance, is poor. (c) Since the homogeneouspacking of an entire capillary becomes increasingly difficult as thecolumn length increases, an improvement of the analytical performance byincreasing the total column length is not practical.

In addition, particle-packed capillary columns equipped with the fritsat both ends frequently causes bubbling at the space between the fritand packed-beds, thus requires additional pressurization to the normalchromatographic operation.

In spite of the fact that the analytical performance of a capillarycolumn is governed by its inner porous structure directly related to thepacking state of the particles, there has been no establishedparticle-packing method which produces the stable and reproduciblepacking state.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 shows the size distribution of mesopores measured for a samplegel prepared according to Example 1.

FIG. 2 shows the electrochromatogram of thiourea obtained using thecapillary column described in Example 1.

SUMMARY OF THE INVENTION

The problem of the present invention is to provide monolithic porousbodies with at least one small dimension, which are useful e.g. assorbents in micro scale separations or as support media for catalysts orimmobilized enzymes.

THIS PROBLEM IS SOLVED BY THE PRESENT INVENTION

The present inventors have found that: A capillary column which exhibitshomogeneous and continuous double pore structure through the wholelength of the capillary can be obtained by the processes of; 1) to forma three-dimensional co-continuous network consisting of an inorganic gelphase and a solvent phase both having average domain size of larger than100 nm via a sol-gel process from a solution precursor containing athermally decomposable component in a capillary with the inner diameterof less than 1 mm, 2) to modify the nanometer-range microstructures byheating the wet gel to decompose said thermally decomposable component,3) to dry and heat-treat the gel to obtain completely inorganic porousmaterial.

A capillary with an inner diameter of less than 1 mm as mentioned aboveis the prefered modification of the invention, e.g. the specialized caseof a confined space with a small dimension in at least one direction asdefined in the problem to be solved by the invention. Accordingly unlessexplicitly stated, a capillary can be replaced by any other confinedspace with a small dimension in at least one direction. In this contexta small dimension is defined as less than 1 mm, preferably between 10and 200 μm. Other examples of confined spaces with a small dimension inat least one direction are: three- or four-sided prisms or thin plates.Typically at least one dimension, e.g. the length of these structures,can be larger, separation capillaries might be one or severalcentimeters long, or even longer. Plates would be thin (less than 1 mm),but could be broader than 1 mm, e.g. one or several centimeters, up toabout 20 cm broad. In all cases the porous formed body is enclosed bysuch a confined space, whereby a liquid tight contact area betweenporous formed body and confined space is provided.

The present invention has been developed based on the above knowledge.The invention provides capillary columns with a well-defined and highlyreproducible internal pore structure through the whole length of thecapillary and with an excellent analytical performance; instead of thosepacked with particles by conventional physical methods which has beendefective in homogeneity, reproducibility and analytical performance.

DETAILED DESCRIPTION OF THE INVENTION

One means of the present invention to attain said object ischaracterized by previously dissolving a thermally decomposable compoundin a reaction solution, forming, from said reaction solution through itssol-gel conversion in a capillary, a gel that comprises a solvent-richphase containing three-dimensionally networked open pores having a meanpore diameter of not smaller than 100 nanometers and an inorganicsubstance-rich skeleton phase containing particles each having finepores on its surface, then heating the wet gel to thermolyze saidthermally decomposable compound existing in the reaction system, andthereafter drying and heating the gel.

In one preferred embodiment of said means, silica SiO₂ is used as theinorganic substance while an amide compound, such as urea, capable ofmaking the reaction system basic through its thermolysis is used as thethermally decomposable, low-molecular compound.

Another means of the present invention also to attain said object ischaracterized by dissolving a water-soluble polymer and a thermallydecomposable compound in an aqueous acidic solution, adding thereto ametal compound having hydrolyzable functional groups to therebyhydrolyze said compound, solidifying the resulting product in acapillary, then heating the wet gel to thereby thermolyze the thermallydecomposable low molecular compound existing in said gel, and thereafterdrying and further heating the gel.

The substance to be added to the starting metal alkoxide is one havingthe function of inducing both sol-gel conversion and phase separation atthe same time. Using this, the reaction system is separated into asolvent-rich phase and a skeleton phase, which are gelled. As thesubstance of that type, preferred is a polymer soluble in solvents, suchas polyethylene oxide, polyvinyl pyrrolidone, polyethylene imine andpolyallylamine.

The metal alkoxide is preferably a silicon alkoxide, which may include,for example, tetramethoxysilane, tetraethoxysilane,methyltrimethoxysilane, ethyltrimethoxysilane and vinyltrimethoxysilane. However, these are not limitative. The metallicelements corresponds to those contained in the desired oxide phase canbe Si, Ti, Zr or Al. Both alkoxides containing single or multiple kindsof metals can be used. The oligomers of the alkoxides, usually up todecamers, can be used as far as they dissolve or disperse homogeneouslyin the solvent alcohol.

The acidity of the aqueous solution used to hydrolyze the metal alkoxideis preferably stronger than 0.001 mol/L of mineral acid such ashydrochloric acid or nitric acid.

The capillary, made of fused silica for example, should have an innerdiameter of less than 1 mm, preferably between 10 and 200 μm. Similarly,instead of capillaries, containers which form inside them thin prisms ofsimilar dimensions or thin plates with a thickness of less than 1 mm canbe used.

The capillary, made of fused silica for example, should have an innerdiameter of less than 1 mm, preferably between 10 and 200 μm. Similarly,instead of capillaries containers which form inside them thin prisms ofsimilar dimensions or thin plates with a thickness of less than 1 mm canbe used.

For the liquid tight junction between rod and capillary, the capillarywall should have high affinity with the gelling silicate componentscomponents in the solidifying solution. For example; (1) materials withsurface hydroxyl groups which can undergo condensation with silanols,(2) relatively polar organic polymer surfaces which can physicallyadsorb silicate oligomers, (3) any other material which issurface-treated with hydrophilic layers; all of these can realize theliquid tight junction. Materials with very high water-repellency, suchas PTFE resin or surfaces modified with fluorine-containing reagents,are not appropriate to make the liquid tight junction by the chemicalmeans described above. In this special case, the use of thermoshrinkingPTFE resin makes it possible to physically liquid tight clad after theformation of the gel body inside the capillary, by heating the resincapillary up to around 300° C. so as to obtain satisfactory cladding.The dimension of the confined space, diameter of a capillary or gapbetween the parallel walls etc., should be in the size range smallerthan 1 mm and preferably smaller than 100 microns.

The hydrolysis and polycondensation reaction is conducted under theconditions of; temperature between 40 and 80° C., reaction time between0.5 and 5 hours. The hydrolysis and polycondensation follows the stepsof; 1) initially transparent solution becomes gradually opaque due tothe phase separation into a gel phase and a pore-forming phase, 2) thewhole solution turns into gel. During the whole reaction steps thewater-soluble polymer is molecularly dissolved in the solution and noeffective precipitation occurs.

One embodiment of the present invention for producing a porous inorganicmaterial, in which the pore structure of the porous inorganic materialcan be most effectively controlled, is sol-gel conversion whichcomprises starting from a metal alkoxide and adding a suitable substanceto said starting compound to thereby give a structure of a solvent-richphase that produces macro-pores.

In the method of the present invention, where a water-soluble polymerand a thermally decomposable compound are dissolved in an aqueous acidicsolution and a metal compound having a hydrolyzable functional group isadded thereto to thereby hydrolyze said metal compound, formed is a gelcomprising a solvent-rich phase and a skeleton phase as separated fromeach other in the capillary. After the product (gel) is solidified andthen ripened for a suitable period of time, the wet gel is heatedwhereby the thermally decomposable compound that has been previouslydissolved in the reaction system is thermally decomposed, resulting inthe increase in the pH of the solvent that is kept in direct contactwith the inner walls of particles constituting the skeleton phase. As aresult, the solvent corrodes said inner wall to thereby change the innersurface of said inner wall into a roughened one, whereby the pore-sizeof said particles is gradually enlarged.

For the gel consisting essentially of silica, the degree of said changein an acidic or neutral region will be very small, but with the increasein the thermolysis to enlarge the basic degree of the aqueous solution,the part constituting each pore is dissolved and re-precipitated to givea more flat part, thereby inducing more active reaction to enlarge themean pore size.

If the gel has only fine and three-dimensionally restrained poreswithout having any macro-pores, even its part capable of being dissolvedunder equilibrated conditions could not produce a dissolved substancecapable of being diffused into the external solution, so that theoriginal fine pore structure will remain in the gel to have a relativelylarge proportion. As opposed to this, if the gel has a solventrich-phase capable of giving macro-pores, it contains a large amount ofonly two-dimensionally restrained fine pores, so that the exchange ofsubstances between said solvent-rich phase and the external aqueoussolution may be effected well frequently in the gel, resulting in theremoval of fine pores with the growth of macro-pores in the gel whilepreventing the entire pore size distribution of the resulting gel frombeing broadened.

In the thermolyzing step, it is effective to put the gel in a closedcondition in order to make the vapor pressure of the thermallydecomposed product saturated and to rapidly make the solvent have asteady pH-value.

Specific examples of the thermally decomposable compound employableherein may include urea, and organic amides such as formamide,N-methylformamide, N,N,-dimethylformamide, acetamide, N-methylacetamide,and N,N-dimethylacetamide. However, as will be mentioned in the Examplesto follow hereinunder, the thermally decomposable compound is notlimited to these, but may be any one capable of making the solvent basicafter its thermolysis, since the pH value of the solvent after thethermolysis (final pH) is an important factor in the method of formingthe mesopores. Similary, thermally-decomposable compounds which generatealternative substances which are capable of dissolving silica, e.g.hydrofluoric acid, can also be used. In addition, those capable ofproducing a compound having the property of dissolving silica, such ashydrofluoric acid, through thermolysis are also usable in the presentinvention. Such pore forming agents or precursors of pore forming agentsare disclosed in WO 95/03 256 and in WO 98/29 350.

The amount of the thermally decomposable compound (precursor of poreforming agent) to be in the reaction system of the present invention mayvary, depending on the type of said compound. For urea, for example, itsamount may be from 0.1 to 2.0 g, preferably from 0.2 to 1.0 g, per 10 gof the reaction system. The heating temperature for the thermolysis ofurea may fall between 60° C. and 200° C., and, after the thermolysis,the final pH of the solvent is preferably from 9.0 to 11.0.

After the dissolving and re-precipitating reaction has reached itssteady condition, the thermolyzing time for obtaining the correspondingpore structure may vary, depending on the size of the intendedmacro-pores and the volume of the reaction system being processed.Therefore, it is important to determine the shortest thermolyzing time,over which the pore structure of the gel is no more substantiallychanged under the processing conditions. For example, where urea is usedas the thermally decomposable compound and the thermolyzing temperaturefalls between 60 C. and 200° C., the thermolyzing temperature fallsbetween 30 days (at 60° C.) to 100 hours (at 200° C.).

From the processed gel, the solvent is evaporated off, whereby the gelis dried to be a dry gel which is coherently attached to the inner wallof the capillary with the inner diameter of less than 1 mm. Since thereis a probability that some starting compounds will still remain in thedry gel, the dry gel is thereafter heated at suitable temperatures tothereby further pyrolyze the remaining organic substances. As a resultof the heat treatment, the intended porous inorganic material is finallyobtained. Generally, the drying is conducted at the temperature between40 and 100° C. for several to several tens hours, whereas theheat-treatment is performed in the temperature range between 300 and700° C.

The porous inorganic materials to be obtained according to the method ofthe present invention have three-dimensionally networked, openthrough-holes of not smaller than 100 nm in diameter, and fine pores offrom 5 to 100 nm in diameter as formed on the inner walls of saidthrough-holes. The porous inorganic materials of the present inventioncan be used in manufacture of chromatography columns, adsorbent andfilters, which, however, are not limitative.

Without further elaboration, it is believed that one skilled in the artcan, using the preceding description, utilize the present invention toits fullest extent. The preferred specific embodiments and examples are,therefore, to be construed as merely illustrative, and not limitative ofthe disclosure in any way whatsoever.

The entire disclosures of all applications, patents, and publicationscited above and below, and of corresponding Japanese Application numberJP-hei 10-11377, filed Jan. 23, 1998, are hereby incorporated byreference.

EXAMPLES Example 1

Firstly, 0.90 g of poly(ethylene oxide) (product No. 85645-2,manufactured by Aldrich, Molecular weight: 10000) and 0.90 g of ureawere dissolved in a 10 g of 0.01 mol/l aqueous solution of acetic acid.Then 4 ml of tetramethoxysilane was mixed with this solution understirring to promote hydrolysis reaction. After a few minutes stirring,the resultant transparent reaction solution was transferred to acapillary with the inner diameter of 0.1 mm (100 μm) and sealed, whichgelled in 30 min at a constant temperature oven kept at 40° C.

The solidified sample was further aged at the same temperature forseveral hours, then heated up to 120° C. and kept at the temperature for1 h under tightly sealed condition. The pH of the solution in contactwith the gel sample was 10.7. The gel was subsequently dried for 3 daysand was heated up to 400° C. with the heating rate of 100° C./h. Withthese processes, a porous amorphous silica filled in a capillary withthe inner diameter of 0.1 mm was obtained.

It was confirmed by the electron microscopic observation that in theporous silica material thus formed in the capillary, uniform macroporeswith a pore size of about 2.0 micrometer were present in aninterconnected manner. In addition, the nitrogen adsorption measurementevidenced the existence of mesopores with average diameter of 25 nm inthe inner wall of the said gel sample. FIG. 1 shows the pore sizedistribution of the mesopores.

In addition, when the porous materials were manufactured under the sameconditions as described above except that the temperature of aging intightly sealed condition was changed to 80° C. or 200° C., thedistributions of the macropores were not affected, but the median sizeof mesopores measured by the nitrogen adsorption varied to about 15 nmand 50 nm for 80° C. and 200° C., respectively. From these results, itwas shown that larger median size of mesopores can be obtained as thetemperature of aging in tightly sealed condition increased.

The capillary column thus prepared, with the effective length of 25 cm,was set in an electrochromatography apparatus, and thiourea was analyzedat the temperature of 20° C. and with the applied electric voltage of 20kV, adopting the mobile phase consisting of (acetonitrile: 50 mM of trisbuffer solution)=80:20 adjusted at pH=8.

The linear velocity of electro-osmotic current obtained under theconditions specified above was 1.19 mm/s, which was comparable to thoseobserved in well-packed conventional particle-packed capillary columns.

FIG. 2 shows the elution peak of thiourea obtained under the conditionsspecified above. The number of theoretical plates calculated from thepeak width was 48000 plates against 25 cm, which is comparable to thevalue of well-packed conventional particle-packed column; 200,000plates/m.

Example 2

The capillary columns were manufactured under identical conditions tothose described in Example 1 except that the amount of urea was 0.45 gto adjust the final value of the solution pH in contact with the gelsample to 9.

The median mesopore sizes of the resultant gels were 15, 25 and 50 nm at80, 120 and 200° C., respectively. These results were in accordance withthose obtained in the Example 1 within the range of experimental error,which implies that the median mesopore size hardly depend on theconcentration of urea, but the widths of the mesopore size distributionbecame broader at all temperatures. These results show that with anincrease in the concentration of urea in the starting solution, themesopore distribution width became narrower and the specific mesoporevolume became larger.

With the capillary columns thus obtained, it was possible to performsimilar electrochromatographic separation of thiourea as described inthe Example 1.

EFFECT OF THE PRESENT INVENTION

As described so far, according to the present invention, it is possibleto manufacture porous materials with controlled pore distribution in acapillary with the inner diameter of less than 1 mm. Presently inventedinorganic porous column has outstanding features owing to itsdouble-pore structure comprising interconnected macropores and tailoredmesopores; the column requires no physical packing procedure for itsproduction and can be suitably applied as a monolithic capillary columnfor electrochromatography, capillary electrophoresis, solid phasemicro-extraction and gas chromatograpy.

What is claimed is:
 1. A process for producing an article comprising an inorganic porous material contained in a container having a confined space of at least one dimension less than 1 mm, which comprises: providing an aqueous acidic solution comprising a water-soluble organic polymer, a thermally decomposable component and a metal compound having thermally hydrolyzable ligands, such that a sol-gel process of hydrolysis and polycondensation is initiated, either before or during the hydrolysis and polycondensation, filling at least part of the confined space of the container with the solution and allowing the hydrolysis and polycondensation to continue such that a three-dimensional co-continuous network of an inorganic gel phase and a solvent phase, both having a diameter of larger than 100 nm is formed from the solution, heating the container with the three-dimensional co-continuous network to decompose the thermally decomposable component, thereby modifying the nanometer-range microstructures, drying and heat-treating the resulting container with the three-dimensional co-continuous network to obtain a completely inorganic, solid porous material in liquid tight contact with the inner wall(s) of the confined space of the container.
 2. The process of claim 1, wherein the metal compound having thermally hydrolyzable ligands is a silicon alkoxide or a soluble or dispersible oligomer thereof which is and the resulting inorganic, solid porous material is of silica.
 3. The process of claim 2, wherein the thermally decomposable compound is urea.
 4. The process of claim 2, wherein the thermally decomposable compound is a compound containing amide or alkylamide ligands.
 5. The process of claim 1, wherein the a container having a confined space of at least one dimension less than 1 mm is a capillary having an inner diameter of less than 1 mm.
 6. The process of claim 2, wherein the a container having a confined space of at least one dimension less than 1 mm is a capillary having an inner diameter of less than 1 mm.
 7. The process of claim 1, wherein the formed inorganic, solid porous material is a three-dimensional network with open macropores of no smaller than 100 nm diameter and mesopores of 5-100 nm formed on the inner walls of the macropores.
 8. The process of claim 1, wherein the water-soluble organic polymer is a polyethylene oxide, polyvinyl pyrrolidone, polyethylene imine or polyallylamine.
 9. The process of claim 2, wherein the a container having a confined space of at least one dimension less than 1 mm is a capillary having an inner diameter of between 10 and 200 μm.
 10. The process of claim 5, wherein the capillary is of a fused silica material.
 11. The process of claim 10, wherein the inners wall of the capillary is treated to provide: a) surface hydroxyl groups which can condense with silanols, b) a polar organic polymer surface which can physically adsorb silicate oligomers, or c) a hydrophilic surface layer.
 12. The process of claim 1, wherein the hydrolysis and polycondensation is conducted at a temperature of 40 to 80° C.
 13. The process of claim 3, wherein 0.1 to 2.0 g of urea is used per 10 g of aqueous acidic solution.
 14. The process of claim 1, wherein the heating of the container with the three-dimensional co-continuous network to decompose the thermally decomposable component is at a temperature of 60 to 200° C.
 15. The process of claim 1, wherein the decomposition of the thermally decomposable component results in raising the pH of the solvent phase.
 16. The process of claim 1, wherein the drying is conducted at a temperature of 40 to 100° C. and the subsequent heat-treating is conducted at 300 to 700° C. to pyrolyze any remaining organic substances. 